胆固醇
氧甾醇
脂筏
细胞生物学
重编程
细菌
微生物学
生物
化学
生物化学
细胞
遗传学
作者
Quan Zhou,Xun Chi,Min Sub Lee,Wei Yuan Hsieh,Jonathan J. Mkrtchyan,An‐Chieh Feng,Cuiwen He,Autumn G. York,Viet L. Bui,Eliza B. Kronenberger,Alessandra Ferrari,Xiao Xu,Allison E. Daly,Elizabeth J. Tarling,Robert Damoiseaux,Philip O. Scumpia,Stephen T. Smale,Kevin J. Williams,Peter Tontonoz,Steven J. Bensinger
标识
DOI:10.1038/s41590-020-0695-4
摘要
Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy. Bensinger and colleagues show that interferons promote host cell resistance to bacterial cytolysins by decreasing cholesterol synthesis and promoting the esterification of cholesterol, which alters the availability of this pool of ‘free’ cholesterol needed for pore formation.
科研通智能强力驱动
Strongly Powered by AbleSci AI